Integrating gene regulatory pathways into differential network analysis of gene expression data

被引:47
作者
Grimes, Tyler [1 ]
Potter, S. Steven [2 ]
Datta, Somnath [1 ]
机构
[1] Univ Florida, Dept Biostat, Gainesville, FL 32611 USA
[2] Univ Cincinnati, Dept Pediat, Cincinnati, OH 45229 USA
基金
美国国家卫生研究院;
关键词
INVERSE COVARIANCE ESTIMATION; RNA-SEQ; DYSREGULATED PATHWAYS; COEXPRESSION NETWORK; ALTERED PATHWAYS; CANCER; IDENTIFICATION; MODEL; ASSOCIATION; GENERATION;
D O I
10.1038/s41598-019-41918-3
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The advent of next-generation sequencing has introduced new opportunities in analyzing gene expression data. Research in systems biology has taken advantage of these opportunities by gleaning insights into gene regulatory networks through the analysis of gene association networks. Contrasting networks from different populations can reveal the many different roles genes fill, which can lead to new discoveries in gene function. Pathologies can also arise from aberrations in these gene-gene interactions. Exposing these network irregularities provides a new avenue for understanding and treating diseases. A general framework for integrating known gene regulatory pathways into a differential network analysis between two populations is proposed. The framework importantly allows for any gene-gene association measure to be used, and inference is carried out through permutation testing. A simulation study investigates the performance in identifying differentially connected genes when incorporating known pathways, even if the pathway knowledge is partially inaccurate. Another simulation study compares the general framework with four state-of-the-art methods. Two RNA-seq datasets are analyzed to illustrate the use of this framework in practice. In both examples, the analysis reveals genes and pathways that are known to be biologically significant along with potentially novel findings that may be used to motivate future research.
引用
收藏
页数:12
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